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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Transcriptional Alterations Related to Neuropathology and Clinical Manifestation of Alzheimer's Disease

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Author(s):
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Silva, Aderbal R. T. [1, 2] ; Grinberg, Lea T. [3, 1] ; Farfel, Jose M. [4, 1] ; Diniz, Breno S. [5] ; Lima, Leandro A. [2] ; Silva, Paulo J. S. [6] ; Ferretti, Renata E. L. [4, 1] ; Rocha, Rafael M. [2] ; Jacob Filho, Wilson [4, 1] ; Carraro, Dirce M. [2] ; Brentani, Helena [7]
Total Authors: 11
Affiliation:
[1] Brazilian Brain Bank, Aging Brain Study Grp, LIM 22, Sao Paulo - Brazil
[2] AC Camargo Hosp, Res Ctr CIPE, Sao Paulo - Brazil
[3] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA - USA
[4] Univ Sao Paulo, Sch Med, Div Geriatr, Sao Paulo - Brazil
[5] Univ Sao Paulo, Sch Med, Dept & Inst Psychiat, LIM 27, Neurosci Lab, Sao Paulo - Brazil
[6] Univ Sao Paulo, Dept Comp Sci, Inst Math & Stat, Sao Paulo - Brazil
[7] Univ Sao Paulo, Sch Med, Clin Pathol Lab, LIM 23, Dept & Inst Psychiat, Sao Paulo - Brazil
Total Affiliations: 7
Document type: Journal article
Source: PLoS One; v. 7, n. 11 NOV 7 2012.
Web of Science Citations: 17
Abstract

Alzheimer's disease (AD) is the most common cause of dementia in the human population, characterized by a spectrum of neuropathological abnormalities that results in memory impairment and loss of other cognitive processes as well as the presence of non-cognitive symptoms. Transcriptomic analyses provide an important approach to elucidating the pathogenesis of complex diseases like AD, helping to figure out both pre-clinical markers to identify susceptible patients and the early pathogenic mechanisms to serve as therapeutic targets. This study provides the gene expression profile of postmortem brain tissue from subjects with clinic-pathological AD (Braak IV, V, or V and CERAD B or C; and CDR >= 1), preclinical AD (Braak IV, V, or VI and CERAD B or C; and CDR = 0), and healthy older individuals (Braak <= II and CERAD 0 or A; and CDR = 0) in order to establish genes related to both AD neuropathology and clinical emergence of dementia. Based on differential gene expression, hierarchical clustering and network analysis, genes involved in energy metabolism, oxidative stress, DNA damage/repair, senescence, and transcriptional regulation were implicated with the neuropathology of AD; a transcriptional profile related to clinical manifestation of AD could not be detected with reliability using differential gene expression analysis, although genes involved in synaptic plasticity, and cell cycle seems to have a role revealed by gene classifier. In conclusion, the present data suggest gene expression profile changes secondary to the development of AD-related pathology and some genes that appear to be related to the clinical manifestation of dementia in subjects with significant AD pathology, making necessary further investigations to better understand these transcriptional findings on the pathogenesis and clinical emergence of AD. (AU)

FAPESP's process: 05/04151-7 - Evaluation of gene expression in Alzheimer´s disease by cDNA microarray technique
Grantee:Aderbal Ruy Teodoro da Silva
Support Opportunities: Scholarships in Brazil - Master